The composition of bacterial species which serves as an essential cofactor in driving chronic intestinal inflammation in susceptible hosts is unclear. We propose to use gnotobiotic C3H mice bearing a defined bacterial flora and infected with Brachyspira hyodysenteriae to examine antigen-specific immune responses to resident flora which modulate the development of colitis. Preliminary data from this B. hyodysenteriae challenge model indicates that not only is intestinal inflammation dependent on the nature of the resident flora, but that alteration in the composition of this flora influences the immunologic bias of host responses subsequent to the onset of colitis. The specific aims of this proposed research are to: (1) define the kinetics of antigen-specific immune responses modulating acute and chronic inflammation in gnotobiotic mice and (2) evaluate the characteristics of the resident flora that are critical in eliciting immune responses in experimental colitis. The candidate has completed a three year residency and board certification in small animal internal medicine and is in the fourth year of a graduate program that will result in a doctorate in immunobiology. Dr. Jergens has an extremely strong background in clinical gastroenterology, and has previously investigated the immunopathologic mechanism(s) of inflammatory bowel disease in dogs and cats. His graduate work has investigated host-bacterial interactions relating to chronic intestinal inflammation in gnotobiotic mice. Throughout his DVM and post-DVM training, Dr. Jergens has participated in research in a variety of animal species with both clinical and research applications. As a veterinary gastroenterologist and immunologist, Dr. Jergens is committed to a career as a clinician investigator in an academic institution. With regards to the environment, the sponsor and collaborators are authorities in immunologic research. The laboratories and other facilities (e.g., gnotobiotic animal facility) in which the candidate is engaged are capable of providing the space, equipment, animal facilities, and support staff required for successful completion of this proposal. The sponsor (MJW has a fully equipped immunology laboratory with technical staff and other research staff (e.g., graduate students and postdoctoral fellow). There are ample opportunities to attend seminars, journal clubs and work-in-progress research meetings during which the applicant can become engaged in scientific discussions.